Effect of an Educational Outreach Program on Prescribing Potential Drug-Drug Interactions

BACKGROUND: The topic of improving prescribing practices is a major focus of many national initiatives, not only to enhance the quality of health care but also to reduce medical care costs. Educational outreach (also known as academic detailing) is a type of postgraduate education where trained clinical consultants meet face-to-face with prescribers to provide one-on-one information. Ideally, such visits promote evidence-based knowledge, create trusting relationships, and induce practice change,  particularly with regard to prescribing potentially interacting medications. OBJECTIVES: To evaluate the effect of an educational outreach program delivered by clinical pharmacists on reducing the rate of prescribing potential drug-drug interactions (DDIs). METHODS: The intervention was a prescriber-directed educational outreach program focused on 25 clinically important DDIs. The effect of the educational outreach was evaluated using a retrospective pre-post study design with a control group was conducted. A total of 19,606 prescribers were educated on the DDIs of interest. A control group of 19,606 prescribers, matched on prescribing volume and who did not receive the educational session were selected. Multivariate regression models were used to assess the impact of the educational program on the rate of prescribing potential DDIs. RESULTS: The 2 groups were significantly different with respect to age, profession, specialty, and geographic region. At baseline, mean DDI rates per 100 drug prescriptions were 0.8 and 0.7 for prescribers who received the educational session and those who did not, respectively. Following delivery of the educational outreach program, mean potential DDI rates increased to 1.46 and 1.53 per 100 precipitant drug prescriptions, an increase of 13.9% and 9.15% for the intervention and control groups, respectively. CONCLUSIONS: The current study was not able to demonstrate a significant beneficial effect of the educational outreach program on reducing the rate of prescribing potential DDIs.

What is already known about this subject • Solomon et al. (2001) examined the efficacy of a targeted oneon-one educational program designed to improve the appropriateness of broad-spectrum antibiotic use. After controlling for baseline prescribing and study interval, the rate of unnecessary use of the 2 target antibiotics (levofloxacin and ceftazidime) was reduced by 41% in the intervention services compared with controls (95% CI, 44%-78%; P < 0.001). The authors concluded that academic detailing is an effective intervention to reduce overutilization of broad-spectrum antibiotics. • Freemantle et al. (2002) estimated the effectiveness of educational outreach visits on United Kingdom general practice prescribing and examined the extent to which practice characteristics influenced outcome. They found that overall educational outreach was associated with a significant improvement in prescribing practice (odds ratio [OR] = 1.24, 95% CI = 1.07-1.42). Interestingly, smaller practices (2 or fewer full-time equivalent practitioners) responded much more favorably (improvement of 13.5%) to educational outreach than larger practices (1.4%).
• Although prescribing potential drug-drug interactions (DDIs) was more likely among physicians in the educational outreach intervention group than those in the control group, the prescriber-directed educational outreach program did not significantly reduce the rate of prescribing potential DDIs (rate ratio = 1.013, 95% CI = 0.997-1.030; P = 0.122). • Academic detailing on diverse therapeutic areas such as multiple medications involved in DDIs may not be as effective as programs related to specific medications or diseases.

What this study adds
I nappropriate prescribing can be associated with suboptimal disease management and increased risks and costs to both patients and health care systems. 1 There is growing evidence that inappropriate prescribing has a significant impact on patient health outcomes, resulting in higher levels of morbidity and mortality 2-4 as well as increased medical care expenditures. [5][6][7] Previous research has attempted to identify important factors that are associated with inappropriate prescribing, including increased rates of prescribing interacting medications. [8][9][10][11] For example, in a review of literature evaluating nonregulatory measures to improve physician-prescribing behavior, inability to keep up with the latest developments in

Participant Selection
Health care providers were identified using the PBM's clinical consultants' contacts database. Of these providers, those in the top 30% were selected to receive the educational outreach visits because they were considered high-volume prescribers, as measured by prescription claim counts and drug costs for the intervention group. A total of 19,606 prescribers were educated on DDIs of interest for this study. The control group, which did not receive the educational outreach intervention, included a stratified random sampling of prescribers who were frequency matched to the intervention group on the number of prescription drug pharmacy claims submitted by their patients at baseline. The intervention and control groups were not stratified by practice site, and both groups were national in scope.

Intervention Procedures
The intervention was a prescriber-directed educational outreach program based on the principles of academic detailing. 19 Training of clinical consultants was delivered jointly by the University of Arizona-based on clinical content developed by the University of Arizona, Albert Einstein College of Medicine-and the University of Washington. Clinical consultants were PharmD trained. Two investigators created a Microsoft PowerPoint presentation and narrated an audiotaped presentation on the development of the clinical content, as well as the clinical information itself. Information on the mechanism of each interaction, along with details related to the actual clinical management was also provided. Summary materials were converted to a document that included the various drug pairs, the clinical consequences of interaction, and alternative management strategies.
Over a 3-month period following the training, clinical consultants visited 19,606 providers to educate them about these interactions. There were approximately 120 clinical consultants in 124 geographical areas across the United States, with most areas incorporating urban or suburban populations. They delivered the educational outreach program to approximately 150 providers every 6 to 8 weeks. There was no requirement that prescribers in either the intervention or control groups had previously prescribed a medication involved in an interaction of interest. Thus, the relevance of the educational intervention likely varied by type of practice and subspecialty. However, all clinicians should be aware of clinically important interactions because they could encounter a patient at risk for an interaction.
Data for determining the frequency of clinically important DDIs were obtained from pharmacy records for the PBM's enrollees. The baseline prescribing patterns of the 25 DDIs were assessed over a pre-intervention period from January 1, 2003, to September 30, 2003. Visits by clinical consultants to prescribers discussing the interactions occurred from October 1, 2003, to December 31, 2003. Postintervention prescribing patterns of clinically important DDIs were assessed terms of new pharmaceutical products and modified formulations of existing ones was found to be associated with inappropriate prescribing practices. 12 Enhancing providers' knowledge of pharmacotherapy can help reduce the rate of prescribing potentially interacting medications. 13 Different interventions have been designed and delivered in an attempt to improve providers' prescribing knowledge. 12 Examples of such interventions include dissemination of printed educational material, group education, feedback of physician-specific prescribing patterns, reminders at the time of prescribing, and one-to-one education. 12 However, evidence regarding the effectiveness of many of these programs is not consistent. 14 There is evidence to suggest that reminder systems and educational outreach visits are usually more effective than other interventions. 15 Educational outreach visits by appropriately trained consultants have consistently demonstrated effectiveness in improving providers' prescribing in clinical practice settings. 12,16 Based on the principles of educational outreach, such visits utilize one-on-one interactive marketing provided by clinical consultants, who have been trained to discuss prescribing decisions with providers in a manner likely to induce an evidence-based practice change. 17 In order to reduce exposure to clinically important drug-drug interactions (DDIs), a partnership was established between a large pharmacy benefit management company (PBM) and 3 academic institutions (University of Arizona, Albert Einstein College of Medicine, and University of Washington), with funding from the Centers for Disease Control and Prevention, to design and deliver a prescriberdirected educational outreach program. The educational outreach intervention involved an audio taped educational program on specific DDIs that clinical pharmacists were able to view at their convenience. Clinical consultants then could provide the entire program, or relevant components of the program, to providers who may benefit from the information based on their previous prescribing habits. This educational outreach focused on 25 clinically important DDIs that are likely to be encountered in ambulatory care settings, which was developed by Malone et al. (2004). 18 The purpose of this study was to evaluate the impact of educational outreach by clinical consultants on reducing the rate of prescribing potential DDIs.

■■ Methods Study Design
This study employed a retrospective pre-post design with a control group to evaluate the impact of prescriber-directed educational outreach program related to clinically important DDIs. The primary outcome was the rate of prescribing interacting medications, defined as the sum of all unique DDIs divided by the total number of drug prescriptions at the prescriber level. over a period of 9 months, starting January 1, 2004, and ending September 30, 2004. The University of Arizona Human Subjects Protection Program approved the protocol for this study.

Statistical Analysis
The 2 study groups, namely the intervention and control groups, were evaluated with respect to age, profession, specialty, geographic region, number of prescription claims, and mean rates of prescribing clinically important potential DDIs at baseline. The number of unique persons for whom a medication was prescribed by each provider was determined and summarized at the group level. No attempt was made to differentiate between interactions involving a single prescriber or interactions involving multiple prescribers.
A multivariate analysis was conducted to assess the impact of the educational program on the rate of prescribing potential DDIs. A Poisson regression model was used to estimate the effect of the educational program on prescribing clinically important DDIs during the follow-up period. The model accounted for baseline DDI rates, baseline number of pharmacy claims, age, profession, specialty, and geographic region. Given the disproportionate representation of warfarin interactions in this study, multivariate analysis was performed with and without warfarin interactions. The results are presented as rate ratios (RR) with 95% confidence intervals (CI). The analysis was conducted using SAS version 9.1 (SAS Institute, Cary, NC).

■■ Results
The prescribers assigned to the intervention and control groups were significantly different in age, profession, specialty, geographic region, and baseline rate of potential DDI prescribing (Table 1). Of particular importance for DDI prescribing, the intervention group had a higher proportion of physicians and cardiologists as opposed to the control group. Though the prescriber groups were matched on number of baseline pharmacy claims, the mean DDI rates per 100 drug prescriptions were 0.8 and 0.7 for prescribers who received the educational session and those who did not, respectively (P < 0.001). Given the extremely large sample size of this study, significant differences between the groups were observed for almost every demographic characteristic evaluated.
During the follow-up period, the rates were 1.46 and 1.53 potential DDIs per 100 precipitant drug prescriptions for prescribers who received the educational session and those who did not, respectively (P = 0.388). Interactions involving warfarin and other anticoagulants accounted for 88% and 85% of all DDIs at baseline in the intervention and nonintervention groups, respectively. During the follow-up period, these interactions accounted for 90% and 88% of all DDIs in the intervention and nonintervention groups, respectively. Interactions involving warfarin with nonsteroidal anti-inflammatory drugs (NSAIDs) accounted for more than 50% of

Baseline Characteristics of Study Participants
interactions involving anticoagulants in both groups during the baseline and follow-up periods. Table 2 illustrates prescribing patterns of the 25 clinically important DDIs in both groups and the percentage of change during the period following the delivery of the educational program. At the end of the educational program, there was a 13.9% increase in prescribing potential DDIs among prescribers receiving the educational sessions compared with 9.15% in the control group. The distribution of DDIs written by the same prescriber during the follow-up period is shown in Table 3. The group of physicians who received the educational sessions had significantly lower rates of DDIs (per 100 precipitant drug prescriptions) involving anti-infective medications and monoamine oxidase inhibitors (P < 0.001). However, this group had significantly higher rates of DDIs involving anticoagulants (P < 0.001).
Multivariate analysis indicated that educational outreach intervention appeared to have no effect on the rate of prescribing potential DDIs (Tables 4 and 5). Compared with the control group, prescribing potential DDIs was more likely among physicians who received the educational outreach intervention (RR = 1.013, 95% CI = 0.997-1.030). The difference between the 2 groups did not reach statistical significance when warfarinrelated interactions were excluded from the analysis. Older prescribers and those with DDIs at baseline were significantly more likely to prescribe potentially interacting medications. Similarly, compared with other specialty groups, cardiologists were significantly more likely to prescribe potentially interacting medications.

■■ Discussion
Improving prescribing practices has become a major focus of the efforts not only to enhance the quality of health care but also to reduce medical care costs. More importantly, prescribing decisions can have a substantial impact on patient safety. Inappropriate prescribing, including prescribing potentially interacting medications, is closely associated with drug-related adverse events. 20 One study showed that 35% of ambulatory care patients using 5 or more medications experienced an

Distribution and Percentage Change of Prescribing Potential DDIs at Baseline and Follow-up
adverse drug event, and 29% required health care services for an adverse drug event. 21 Given that DDIs are often predictable (based on previous reports, clinical studies, and an understanding of pharmacological principles), enhancing prescribers' knowledge can be critical to reducing the rate of prescribing potentially interacting medications. 20 Educational outreach visits to prescribers by clinical consultants, who are appropriately trained, is one method that has been shown to be effective in inducing prescribing patterns.
The current study evaluated the impact of an educational outreach intervention delivered by clinical pharmacists on reducing the rate of clinically important DDIs. This study was not able to demonstrate a beneficial effect of the educational outreach program on reducing the rate of prescribing potential DDIs. This finding is consistent with evidence from past research that reported varying levels of effectiveness and/or persistence of effect from prescriber educational programs. [22][23][24][25][26][27][28][29][30] However, the lack of effect may be due to several factors that are important in detecting significant changes in prescribing practices.
The educational outreach program selected providers with the highest prescribing rates and the highest medication costs instead of those with the highest rates of prescribing selected potential DDIs. Focusing on prescribers who are in most need of an educational outreach program is important to yield substantial savings or improvement in care. 31 For example, Avorn and Soumerai (1983) found that educational outreach visits targeting physicians who were moderate to heavy prescribers of 1 or more problematic drug categories resulted in a 14% reduction in prescribing these drugs compared with the control group (P = 0.0001). 16 Similarly, in a statewide educational program to improve antibiotic prescribing in office practice, Schaffner et al. (1983) reported a reduction of 18% in the number of doctors prescribing these medications, 44% in the number of patients per doctor receiving these drugs, and 54% in the number of prescriptions written per doctor. 32 A pilot study evaluating the use of a clinical pharmacist as a therapeutics adviser to modify antibiotic prescribing by general practitio-ners showed that academic detailing was successful in modifying prescribing patterns and decreasing prescription numbers and costs. 33 In particular, physicians in the intervention group prescribed significantly more antibiotics than were recommended for first-line treatment in the post-vs. predetailing periods, whereas physicians in the control group prescribed significantly more drugs that were not recommended.
In the present study, educational outreach visits pertaining to DDIs were only offered once by clinical consultants. Other educational programs were delivered to the intervention prescribers over time besides the one specific to interactions. Yet, according to Soumerai and Avorn (1990), repetition and reinforcement visits are essential to increasing success rates of educational outreach programs. 19 Given the rapid pace of medical knowledge and an ever-evolving health care system, repeated sessions may be necessary to sustain changes in behavior. It is also recommended that each visit focus on a small number of important messages, rather than communicate too many complex ideas, as attempting to do so may fail to achieve retention of the most important points. 19 In a study examining the effect of academic detailing as a method of implementing a clinical guideline in general practice, Witt et al. (2004) reported no effect of educational outreach visits and suggested that when visits are not followed by any other intervention, sustaining behavioral change is unlikely because there was nothing to remind physicians of the visit. 26 While repetition is important, providing feedback of improved behavior with reinforcement can also promote effective academic detailing. 19 For instance, when prescribers discuss their experiences with implementing recommended changes in prescribing behavior during followup visits, detailers can verbally encourage and applaud their successes as well as discuss problem cases and their resolutions. 19 Other studies showed that a reinforcement visit would be necessary to maintain changes in behavior and perhaps to engage physicians not captured in the initial encounter. 29,34 Data also supported a doubling in the reduction of inappropriate prescribing among physicians who received follow-up visits compared with those who received only 1 visit. 35

Distribution of Drug-Drug Interactions Written by the Same Prescriber During Follow-up
surprising given the strength of the electronic medical record alerting intervention. 28 Another example is the perception of physicians. For instance, if the information presented during the educational outreach visit is not new, or that physicians had other ways of obtaining the information, they may develop doubts about the independence and objectivity of the information. This, in turn, may limit the possibilities of detecting positive effects from educational outreach visits. 36 External environmental factors can also impose an influence on prescribing patterns. 37 Figueiras et al. (2001) reviewed 8 studies of educational programs designed to improve prescription practices in ambulatory care and concluded that in 7 of these studies the difference between pre-and postmeasurements may be due to the statistical law of regression of the mean and to other factors not related to educational outreach interventions. 38 In addition, temporal variations of medication use might be affected by certain external variables, such as seasonal variations of disease frequency, marketing by pharmaceutical companies, safety issues, and regulatory policies. 38 Prescriber characteristics may play a role in the lack of effect of the educational outreach program. In this study, older prescribers were significantly more likely to prescribe potentially interacting medications (RR = 1.002, P < 0.001, 95% CI = 1.002-1.002), but this difference may not be clinically meaningful. Furthermore, specialty groups and geographic regions varied significantly across groups (Table 4). In particular, cardiologists were significantly more likely to prescribe potentially interacting medications when compared with other physician specialty groups, which might be attributed to the specific set of DDIs of interest used by the educational program. This finding was contrary to what was reported by Soumerai and Avorn (1987), who found no statistical differences in the mean program effect between older versus younger physicians and across various physician specialty groups. 35 Other studies have also evaluated the effect of practice characteristics. Freemantle et al. (2002) found that practices with 2 or fewer practitioners showed a substantial reaction to the effect of educational outreach visits, whereas the effect in larger practices was modest and statistically nonsignificant. 25 While the effect of practice characteristics was not examined in this study, it may be speculated that practitioners in larger practices may find it harder to influence change because of concerns regarding peer perceptions. Such influence may have had an impact on the results, thereby masking the effectiveness of the educational outreach visits. Therefore, it is recommended that future studies include prescriber characteristics and practice characteristics to assist in determining the effect of educational outreach visits on DDIs.
Lastly, detecting significant impact of educational outreach programs can also depend on the structure of the program as well as the design and content of the educational outreach materials. Offering practical alternatives to the target medications and minimizing the effect of the detailer's personal style through standardizing the educational encounter can Educational outreach interventions usually take place within an environment that includes multiple factors, each with the potential to influence prescribing patterns. 15 Factors within the immediate work environment, or within the external environment, can have an important impact on the effectiveness of educational outreach interventions. One example is the computerized decision support systems. In a study evaluating the effectiveness of electronic medical record alerts for selected medications that interact with warfarin, Feldstein et al. (2006) found no significant improvement in the rate of prescribing potential DDIs as a result of academic detailing. 28 The authors suggested that the absence of an additional intervention effect from the educational visits may not be especially  groups was no longer significant. Interestingly, cardiologists were more likely to prescribe potentially interacting medications than physicians of other specialties, even when warfarin interactions were excluded from the analysis.

Limitations
There are several limitations to this study. A major limitation is its quasi-experimental design and the lack of random selection of prescribers for the educational outreach program. Cardiologists, who are more likely to prescribe anticoagulants, were over-represented in the intervention group. Also, the educational outreach intervention focused on the optimal management of potential anticoagulant-related DDIs, rather than outright discontinuation of medication. Despite the groups being matched with respect to prescribing volume, other differences with respect to demographic characteristics were noted. Furthermore, the educational program did not focus specifically on only those prescribers with a history of prescribing 1 or more of the interaction medications. Delivering a successful educational outreach program partially depends on the appropriateness of the target population, 19 so selecting prescribers based on prescription volume and cost at baseline, instead of their prescribing patterns of potential DDIs, was probably not conducive to detecting a positive intervention effect. Contamination between study groups might have also been a potential reason for the lack of effect of educational outreach interventions. 38 Contamination may occur when physicians from different intervention groups work closely and share information about the interaction. 38 The study did not attempt to control for intervention and controls residing within the same practice setting. This expectedly may result in a reduction of the measured effectiveness of the intervention. Finally, the intervention may have been more effective if educational interventions occurred solely with prescribers who were involved in a potential interaction exposure and this information was included as a part of the intervention.

■■ Conclusion
The current educational outreach intervention did not significantly alter potential DDI prescribing. There are numerous potential causes for the lack of effect, including selection bias as a result of prescriber targeting and matching criteria, type of intervention content, and absence of reinforcing messages or prescriber feedback.
Although clinical consultants have shown to be a novel and potentially effective method for delivering educational outreach content, future educational outreach efforts should incorporate reinforcement and feedback in the messaging and should tailor the content to the specific needs and relevance of prescribers.
contribute to the success of educational outreach visits. 17,39 In this study, the majority of DDIs were attributed to warfarin and other anticoagulants, a finding that is consistent with other studies of DDIs. 28,40 To further investigate whether the disproportionate representation of warfarin interactions might be associated with biased estimates, a multivariate analysis was performed with and without warfarin interactions (Tables 4 and 5). The results from the analyses were different; prescribers in the intervention group were significantly more likely to prescribe potentially interacting medications than the control group, when warfarin interactions (specifically with NSAIDs) were included. However, when those interactions were removed, the difference in prescribing behavior between the intervention and control